Synthetic, degradable polymeric networks have found utility as biomaterials in a variety of medical applications. For example, degradable polymeric networks can be used as carriers for delivery of therapeutic agents, such as gene therapy agents, drugs, and biocompatible organic compounds that modify cellular function. In particular, degradable polymeric networks can serve as conduits for guided tissue regeneration, such as in wound healing. Further, degradable polymeric networks can serve as supportive scaffolding for cells, such as in bone regeneration and repair. Still further, degradable polymeric networks can serve as stimulants of desired cellular responses and as specific substrates for targeted cell adhesion, among other cellular applications.
Degradable polymeric networks that are useful in biomedical applications are typically based on polymers that are desirably nontoxic and biocompatible. Poly(ethylene glycol) (PEG), a hydrophilic polyether, is one such polymer. Water-soluble polymers such as PEG, have been investigated extensively in recent years for use as nontoxic, biocompatible, protein repulsive, noninflammatory, and nonimmunogenic modifiers for drugs, proteins, enzymes, and surfaces of implanted materials. The solubility of PEG in water as well as a number of common organic solvents facilitates its modification by a variety of chemical reactions and makes it useful for binding water-insoluble or poorly water-soluble molecules and rendering them water-soluble.
Formation of a degradable polymeric network from PEG typically involves chemical modification of the PEG in order to form a cross-linkable macromer. The chemical modification may take a variety of forms, typically involving bonding the PEG to a cross-linkable moiety. When the macromers are cross-linked together, a polymeric network is formed that includes the cross-linkable moieties, as well as PEG polymer units. Polymeric networks based on PEG may differ in their properties, depending for example on the nature of the cross-linking and the presence of any co-polymers.
Poly(ethylene glycol) (PEG) based macromers have been extensively investigated for use in hydrogel preparation. Hydrogels swell in water and have been investigated particularly as carriers of therapeutic agents. Hydrogels have the advantages that they diminish non-specific adherence of carried agents to cells. Thus, they can be made cell-adhesion specific through the introduction of specific attached molecules, or ligands.
Typically, PEG macromers have been based on (meth)acrylation of PEG based polymers, where the (meth)acrylate group functions as the cross-linkable moiety. PEG di-(meth)acrylate has been cross-linked by photoirradiation, among other methods. The photo-cross-linking of PEG acrylates has been extensively explored as a method of coating PEG onto surfaces of polymeric materials and biological tissues. A disadvantage of PEG acrylates, such as PEG methacrylates, for use in forming a degradable polymeric network is that hydrolysis of a PEG acrylate macromer liberates ethylene glycol and an acrylic acid, such as methacrylic acid. Methacrylic acid is toxic and thus not biocompatible. Further, PEG mono- and di-(meth)acrylates have a tendency to form clumped polymeric networks, due to the cross-linkable moiety being present at one or both ends of the macromer.
An alternative type of PEG macromer based on the photodimerization of cinnamylidene groups has also been synthesized. This light-sensitive PEG macromer has been cross-linked by long wavelength (>300 nm) UV irradiation, however, the photo-cross-linked PEG hydrogels can undergo photoscission with UV irradiation at 254 nm. Various proteins such as myoglobin, hemoglobin, lactate dehydrogenase, and organophosphorous hydrolase have been immobilized into the photosensitive hydrogels and their stability has been demonstrated.
Nothwithstanding the above teachings, it is desirable to provide PEG-based polymeric networks that are biodegradable, have desired mechanical properties in both wet and dry states, and that degrade into non-toxic degradation products.